A Novel Interleukin-17 Receptor-like Protein Identified in Human Umbilical Vein Endothelial Cells Antagonizes Basic Fibroblast Growth Factor-induced Signaling

Autor: Scott M. Wasserman, Ruey-Bing Yang, Mary E. Gerritsen, James N. Topper, Chi Kin Domingos Ng, László G. Kömüves
Rok vydání: 2003
Předmět:
MAPK/ERK pathway
Umbilical Veins
Angiogenesis
Basic fibroblast growth factor
Fibroblast growth factor
Biochemistry
chemistry.chemical_compound
Cell Movement
Genes
Reporter
Tumor Cells
Cultured
Tissue Distribution
Cloning
Molecular
Luciferases
Receptor
Cells
Cultured
In Situ Hybridization
Receptors
Interleukin-17
Reverse Transcriptase Polymerase Chain Reaction
Recombinant Proteins
Fibroblast Growth Factor 2
Mitogen-Activated Protein Kinases
Signal transduction
Cell Division
Plasmids
Protein Binding
Signal Transduction
Blotting
Western
Molecular Sequence Data
Neovascularization
Physiologic
Biology
Transfection
Cell Line
Animals
Humans
Amino Acid Sequence
RNA
Messenger
Molecular Biology
Mitogen-Activated Protein Kinase Kinases
Sequence Homology
Amino Acid
HEK 293 cells
Receptors
Interleukin
Cell Biology
Fibroblast growth factor receptor 4
Blotting
Northern
Precipitin Tests
Receptors
Fibroblast Growth Factor
Molecular biology
Protein Structure
Tertiary
chemistry
Endothelium
Vascular
Zdroj: Journal of Biological Chemistry. 278:33232-33238
ISSN: 0021-9258
DOI: 10.1074/jbc.m305022200
Popis: We have previously utilized a combination of high throughput sequencing and genome-wide microarray profiling analyses to identify novel cell-surface proteins expressed in human umbilical vein endothelial cells. One gene identified by this approach encodes a type I transmembrane receptor that shares sequence homology with the intracellular domain of members of the interleukin-17 (IL-17) receptor family. Real-time quantitative PCR and Northern analyses revealed that this gene is highly expressed in human umbilical vein endothelial cells and in several highly vascularized tissues such as kidney, colon, skeletal muscle, heart, and small intestine. In addition, we also found that it is also highly expressed in the ductal epithelial cells of human salivary glands, seminal vesicles, and the collecting tubules of the kidney by in situ hybridization. This putative receptor, which we have termed human SEF (hSEF), is also expressed in a variety of breast cancer tissues. In co-immunoprecipitation assays, this receptor is capable of forming homomeric complexes and can interact with fibroblast growth factor (FGF) receptor 1. Overexpression of this receptor inhibits FGF induction of an FGF-responsive reporter gene in human 293T cells. This appears to occur as a result of specific inhibition of p42/p44 ERK in the absence of upstream MEK inhibition. This inhibitory effect is dependent upon a functional intracellular domain since deletion mutants missing the IL-17 receptor-like domain lack this inhibitory effect. These findings are consistent with the recent discovery of the zebrafish homologue, Sef (similar expression to fgf genes), which specifically antagonizes FGF signaling when ectopically expressed in zebrafish or Xenopus laevis embryos. Based on sequence and functional similarities, this novel IL-17 receptor homologue represents a potential human SEF and is likely to play critical roles in endothelial or epithelial functions such as proliferation, migration, and angiogenesis.
Databáze: OpenAIRE
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